(S)-methyl (4-chlorobenzoyl)phenylalaninate | 59490-38-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-methyl (4-chlorobenzoyl)phenylalaninate
• 英文别名: N-p-Chlorbenzoylphenylalanin-methylester；N-(p-chlorobenzoyl)phenylalanine methyl ester；methyl (2S)-2-[(4-chlorobenzoyl)amino]-3-phenylpropanoate
• CAS: 59490-38-9
• 化学式: C₁₇H₁₆ClNO₃
• 分子量: 317.772
• InChiKey: KREXJITYFSDYJS-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-methyl (4-chlorobenzoyl)phenylalaninate 在 Hoveyda-Grubbs catalyst second generation 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.3h， 生成 4-chloro-N-((S)-1-oxo-1-(((S,E)-6-oxo-1-phenylhept-4-en-3-yl)-amino)-3-phenylpropan-2-yl)benzamide
  参考文献：
  名称：

  Optimization Strategy of Novel Peptide-Based Michael Acceptors for the Treatment of Human African Trypanosomiasis

  摘要：

  This paper describes an optimization strategy of the highly active vinyl ketone 3 which was recognized as a strong inhibitor of rhodesain of Trypanosoma brucei rhodesiense, endowed with a k(second) value of 67 X 10(6) M-1 min(-1) coupled with a high binding affinity (K-i = 38 pM). We now report a new structure-activity relationship study based on structural variations on the P3, P2, and P1' sites which led us to identify two potent lead compounds, i.e., vinyl ketones 4h and 4k. Vinyl ketone 4h showed an impressive potency toward rhodesain (k(second) = 8811 X 10(5)) coupled to a good antiparasitic activity (EC50 = 3.6 mu M), while vinyl ketone 4k proved to possess the highest binding affinity toward the trypanosomal protease (K-i = 0.6 pM) and a submicromolar antiparasitic activity (EC50 = 0.67 mu M), thus representing new lead compounds in the drug discovery process for the treatment of Human African Trypanosomiasis.

  DOI：

  10.1021/acs.jmedchem.9b00908
• 作为产物：
  描述：

  2-[(4-氯苯甲酰基)氨基]-3-苯丙酸 在 (S)-2-(2-((2,6-diisopropylphenyl)carbamoyl)pyrrolidin-1-yl)-4-(pyrrolidin-1-yl)pyridine 1-oxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 (S)-methyl (4-chlorobenzoyl)phenylalaninate
  参考文献：
  名称：

  2-取代的 DMAP-N-氧化物作为酰基转移催化剂的合理设计：吖内酯的动态动力学拆分

  摘要：

  提出了一种新概念，即手性 2-取代 DMAP 转化为其 DMAP-N-氧化物可以显着提高催化活性，并且仍可用作酰基转移催化剂。一种由l-脯氨酰胺衍生的新型手性2-取代DMAP-N-氧化物被合理设计、简便合成并应用于吖内酯的动态动力学拆分。使用简单的甲醇作为亲核试剂，可以高产率（高达 98% 的产率）和对映选择性（高达 96% ee）生产各种 L-氨基酸衍生物。此外，还获得了α-氘标记的l-苯丙氨酸衍生物。实验和 DFT 计算表明，在 2-取代的 DMAP-N-氧化物中，氧原子充当亲核位点，NH 键充当 H 键供体。反应的高对映选择性受空间因素的控制，苯甲酸的加入通过参与氢键的构建降低了活化能。理论化学研究表明，只有充分考虑手性催化剂的攻击方向，才能得到正确的计算结果。这项工作为利用吡啶环的 C2 位置和开发手性 2-取代 DMAP-N-氧化物作为有效的酰基转移催化剂铺平了道路。

  DOI：

  10.1021/jacs.0c09075

文献信息

• Copper + Nickel-in-Charcoal (Cu−Ni/C): A Bimetallic, Heterogeneous Catalyst for Cross-Couplings
  作者：Bruce H. Lipshutz、Danielle M. Nihan、Ekaterina Vinogradova、Benjamin R. Taft、Žarko V. Bošković

  DOI：10.1021/ol801676u

  日期：2008.10.2

  catalyst composed of copper and nickel oxide particles supported within charcoal has been developed. It catalyzes cross-couplings that traditionally use palladium, nickel, or copper, including Suzuki-Miyaura reactions, Buchwald-Hartwig aminations, vinylalane alkylations, etherifications of aryl halides, aryl halide reductions, asymmetric conjugate reductions of activated olefins, and azide-alkyne "click"

  已经开发出一种由负载在木炭中的铜和氧化镍颗粒组成的新型多相催化剂。它催化传统上使用钯、镍或铜的交叉偶联反应，包括 Suzuki-Miyaura 反应、Buchwald-Hartwig 胺化、乙烯基丙烷烷基化、芳基卤化物的醚化、芳基卤化物还原、活化烯烃的不对称共轭还原和叠氮炔”点击”反应。
• Nickel-on-Charcoal-Catalyzed Reductions of Aryl Chlorides
  作者：Bruce H. Lipshutz、Takashi Tomioka、Kimihiko Sato

  DOI：10.1055/s-2001-14636

  日期：——

  Exposure of (functionalized) aryl chlorides to catalytic quantities of nickel-on-charcoal in the presence of stoichiometric amounts of Me2NH · BH3/K2CO3 in refluxing acetonitrile leads to high yields of reduced arenes. PCBs are also reduced under these conditions. The method is highly tolerant of moisture.

  将（功能化）芳基氯化物暴露于催化量的碳灰镍，并在恒温回流的乙腈中加入化学计量的 Me2NH · BH3/K2CO3，可以得到高产率的还原芳烃。在这些条件下，PCB 也能被还原。该方法对水分的耐受性非常高。
• Enzymic asymmetric synthesis of .alpha.-amino acids. Enantioselective cleavage of 4-substituted oxazolin-5-ones and thiazolin-5-ones
  作者：Joyce Z. Crich、Rosario Brieva、Peer Marquart、Rui Lin Gu、Steffen Flemming、Charles J. Sih

  DOI：10.1021/jo00064a010

  日期：1993.6

  A general enzymatic asymmetric synthesis of L-alpha-amino acids has been developed. This method entails the use of the Pseudomonas cepacia lipase (P-30) to catalyze the enantioselective methanolysis of a variety of 4-substituted 2-phenyloxazolin-5-one derivatives in a nonpolar organic solvent to furnish optically-active N-benzoyl-L-alpha-amino acid methyl esters (ee = 66-98%), which in turn is subjected to a protease-catalyzed kinetic resolution yielding enantiomerically-pure N-benzoyl-L-alpha-amino acids. This synergistic coupling of two enzymes allows the ready preparation of L-alpha-amino acids of high enantiopurity in yields greater than 50%, an inherent advantage over conventional resolution procedures. Two proteases were found to catalyze the enantioselective hydrolysis of a variety of 4-substituted 2-phenylthiazolin-5-one derivatives to give N-(thiobenzoyl)-L-alpha-amino acids of high optical purity.
• Development of Nickel-on-Charcoal as a ‘‘Dirt-Cheap’’ Heterogeneous Catalyst: A Personal Account
  作者：Bruce H. Lipshutz

  DOI：10.1002/1615-4169(20010430)343:4<313::aid-adsc313>3.0.co;2-a

  日期：2001.4.30
• Discovery of a novel GRPR antagonist for protection against cisplatin-induced acute kidney injury
  作者：Ming-jun Yu、Chao Li、Sheng-song Deng、Xiao-ming Meng、Ri-sheng Yao

  DOI：10.1016/j.bioorg.2022.105794

  日期：2022.7